scholarly journals Upregulation of cyclase-associated actin cytoskeleton regulatory protein 2 in epithelial ovarian cancer correlates with aggressive histologic types and worse outcomes

2020 ◽  
Vol 50 (6) ◽  
pp. 643-652 ◽  
Author(s):  
Masataka Adachi ◽  
Yohei Masugi ◽  
Ken Yamazaki ◽  
Katsura Emoto ◽  
Yusuke Kobayashi ◽  
...  

Abstract Objective Cyclase-associated actin cytoskeleton regulatory protein 2 (CAP2) regulates actin dynamics to control cell cycles and cell migration. CAP2 overexpression contributes to cancer progression in several tumor types; however, the role of CAP2 expression in ovarian cancer remains unclear. This study aimed to clarify the significance of CAP2 expression in epithelial ovarian tumor. Methods We evaluated CAP2 expression in ovarian cancer cell lines using quantitative real-time polymerase chain reaction, western blotting and immunocytochemistry and examined the effect of CAP2 silencing in migration and proliferation assays. CAP2 immunohistochemistry was conducted using tissue specimens from 432 ovarian carcinoma patients; a further 55 borderline and benign 65 lesions were analyzed. CAP2 expression levels were defined as low, intermediate or high, for correlation analysis with clinicopathological factors. Results CAP2 expression was significantly higher in cell lines from Type II ovarian cancer than in those in Type I, and knockdown of CAP2 showed decreased migration and proliferation. Higher levels of CAP2 expression in human tissues were associated with Type II histology, residual lesion, lymph node metastasis, ascites cytology and higher clinical stage. High CAP2 expression levels were observed in 26 (23.4%) of 111 Type II ovarian cancers and in 16 (5.0%) of 321 Type I cancers but not in any borderline or benign lesions. Multivariate analyses showed that CAP2 expression in ovarian cancer is an independent prognostic factor for recurrence-free survival (P = 0.019). Conclusion CAP2 expression is upregulated in aggressive histologic types of epithelial ovarian cancer and serves as a novel prognostic biomarker for patient survival.

2013 ◽  
Vol 131 (1) ◽  
pp. 52-58 ◽  
Author(s):  
Björg Kristjansdottir ◽  
Kristina Levan ◽  
Karolina Partheen ◽  
Karin Sundfeldt

2013 ◽  
Vol 42 (s1) ◽  
pp. 28-29
Author(s):  
J. Alcazar ◽  
J. Utrilla-Layna ◽  
J. Minguez ◽  
M. Jurado

Author(s):  
Ying Chen ◽  
Kaixu Yu ◽  
Qingqing Zhu ◽  
Weicheng Tang ◽  
Dan Chen ◽  
...  

Objective To determine the relative risk of suicide and accidental death among patients with ovarian cancer to that of the general population, and to identify risk factors associated with suicide and accidental death. Design The surveillance, epidemiology, and end results (SEER) registry provided ovarian cancer data from 18 registries. Setting Surveillance, Epidemiology, and End Results database. Population The study population comprised 149,204 patients. Methods The standardized mortality ratios (SMRs) were calculated and Fine-Gray models were fitted, with stratifications on demographic and tumor-related characteristics. Main outcome measures The standardized mortality ratios. Results Women with ovarian cancer had a higher risk of suicide and accidental death than the cancer-free group (SMR=1.86; 95% CI [1.54-2.25] and SMR=1.54; 95% CI [1.39-1.71]). Subgroup analysis indicated that only patients with type II epithelial ovarian cancer (SMR=2.31; 95% CI [1.83-2.91]) had an increased risk of suicide, and those with type I and type II epithelial ovarian cancer (SMR=1.65; 95% CI [1.39-1.97] and SMR=1.49; 95% CI [1.30-1.70]) were at a higher risk of accidental death. Patients with ovarian cancer who were younger, white, diagnosed with high-grade, non-metastatic cancer and pelvic exenteration were at a higher risk of suicide. Additionally, pelvic exenteration increased the risk of suicide but not the risk of accidental death among these women. Conclusion Women with ovarian cancer had a higher risk of suicide and accidental death compared with the general population. Clinicians should identify high-risk subgroups of ovarian cancer patients for suicide and accidental death as early as possible, with appropriate prevention strategies.


2019 ◽  
Vol 20 (4) ◽  
pp. 1161-1169 ◽  
Author(s):  
Wilasinee Nhokaew ◽  
Pilaiwan Kleebkaow ◽  
Nipon Chaisuriya ◽  
Chumnan Kietpeerakool

2017 ◽  
Vol 90 ◽  
pp. 225-233 ◽  
Author(s):  
Dong Liu ◽  
Lin Zhang ◽  
Nekitsing Indima ◽  
Kun Peng ◽  
Qianyu Li ◽  
...  

2019 ◽  
Vol 28 (1) ◽  
pp. 63-9
Author(s):  
Nugraha Utama Pelupessy ◽  
Andrijono Andrijono ◽  
Bambang Sutrisna ◽  
Alida Roswita Harahap ◽  
Mpu Kanoko ◽  
...  

BACKGROUND Ovarian cancer is a heterogeneous disease, and most patients are diagnosed at an advanced stage. Epithelial ovarian cancer type II is characterized by rapid tumor growth and is genetically more labile than type I. This study was aimed to demonstrate the prognostic value of CSC by using the markers CD133, CD44, and ALDH1A1 in EOC.METHODS Clinicopathological and demographic data were collected from medical records. The markers CD133, CD44, and ALDH1A1 were examined with flow cytometry and immunohistochemistry. Cancer stem cell (CSC) marker expression in patients with ovarian cancer types I and II were related to chemotherapy and survival. In multivariate analysis, the prognosis model was tested for ten months.RESULTS The largest demographic consisted of patients aged ≥45 years, with stage I, poor differentiation, and type II, of which there were 40 samples (72.7%), 23 samples (41.8%), 30 samples (54.5%), and 16 samples (29.1%), respectively. There is a high correlation between the 10-month chemotherapy response and the 4 variables, i.e., age ≥45 years, type II, stage III–IV, and CD44, with an ROC of 80.75% and a post-test probability of 82.5%. Using the ROC curve, the highest chemoresistance score was 0.841, based on the combination of CSCs markers and clinicopathological factors, that is stage III–IV, age ≥45 years, poor differentiation, type II, negative CD133, high CD44, and high ALDH1A1.CONCLUSIONS CSC (CD133, CD44, and ALDH1A1) markers and clinicopathological factors are prognostic of epithelial ovarian cancer.


2015 ◽  
Vol 136 (2) ◽  
pp. 205-211 ◽  
Author(s):  
Kira Philipsen Prahm ◽  
Mona Aarenstrup Karlsen ◽  
Estrid Høgdall ◽  
Nikolai Madrid Scheller ◽  
Lene Lundvall ◽  
...  

2021 ◽  
Vol 11 ◽  
Author(s):  
Chang Xiong ◽  
Zhongfeng Sun ◽  
Jinjin Yu ◽  
Yaying Lin

BackgroundOf gynecologic malignancies, ovarian cancer is the leading cause of death, mainly due to the lack of sensitive tumor markers, which means it almost always presents at an advanced stage. Exosome Component 4 (EXOSC4) is involved in RNA degradation, but its role in epithelial ovarian cancer (EOC) is unclear.MethodsThe expression levels of EXOSC4 in EOC and normal ovarian tissue specimens were determined by immunohistochemical staining. The overall survival (OS) and progression-free survival (PFS) of patients with EOC were evaluated after patients were classified into high and low EXOSC4 expression groups, and the Cox regression model was established to identify independent predictors of patient prognosis. The effects of EXOSC4 on proliferation, colony formation, migration, and invasion were examined in the SKOV-3 and HO8910 cell lines by lentivirus-mediated shRNA knockdown. Flow cytometry was used to detect cell cycle changes. The mRNA levels of cyclin D1, CDK4, and c-myc were detected by RT-PCR. The protein expression levels of β-catenin, cyclin D1, CDK4, c-myc, vimentin, N-cadherin, and E-cadherin were assessed by western blot. Wnt/β-catenin activation was measured by TCF/LEF reporter assay.ResultsEXOSC4 was significantly elevated in EOC tissues and cell lines. High EXOSC4 expression was correlated with the International Federation of Gynecology and Obstetrics (FIGO) stage and pathological grade, and identified as an independent predictor of shorter OS and PFS. EXOSC4 knockdown suppressed proliferation, migration, and invasion in EOC cell lines. Cells were arrested at G0/G1 phase after EXOSC4 knockdown. The mRNA levels of cyclin D1, CDK4, and c-myc were decreased. β-catenin, cyclin D1, CDK4, c-myc, vimentin, and N-cadherin protein expression levels were reduced, while those of E-cadherin was increased. Wnt/β-catenin activity was suppressed after the EXOSC4 knockdown.ConclusionsEXOSC4 is involved in EOC. Knockdown of EXOSC4 can inhibit the proliferation, migration, and invasion ability of EOC by suppressing the Wnt pathway. EXOSC4 is expected to be a novel biomarker and molecular target in EOC.


2013 ◽  
Vol 23 (5) ◽  
pp. 815-822 ◽  
Author(s):  
Xiaoxiang Chen ◽  
Jing Zhang ◽  
Wenjun Cheng ◽  
Doo Young Chang ◽  
Jianfei Huang ◽  
...  

ObjectiveMost patients with epithelial ovarian cancer achieve a complete clinical remission (CCR) with normal CA-125 but will still relapse and die from their disease. The present study was designed to determine whether CA-125 levels before, during, and after primary treatment provide prognostic information for both type I and type II ovarian cancer.MethodsIn this retrospective study, we identified 410 patients with epithelial ovarian cancer who had achieved a CCR between 1984 and 2011. A Cox proportional hazards model and log-rank test were used to assess associations between the nadir CA-125, histotype, and prognosis.ResultsThe baseline serum CA-125 concentration was higher in patients with type II ovarian cancer than in those with type I ovarian cancer (P < 0.001). The nadir CA-125 was an independent predictor of progression-free survival (PFS; P < 0.001) and overall survival (OS; P = 0.035) duration. The PFS and OS durations were 21.7 and 79.4 months in patients with CA-125 of 10 U/mL or less and 13.6 and 64.6 months in those with CA-125 of 11 to 35 U/mL, respectively (P = 0.01 and P = 0.002, respectively). Histotype was an independent predictor of PFS (P = 0.041): the PFS and OS durations of the patients with type I ovarian cancer were longer than those of the patients with type II ovarian cancer (P < 0.001 and P < 0.001, respectively).ConclusionsThe nadir CA-125 and histotype are predictive of PFS and OS durations in patients with ovarian cancers who experienced a CCR. Progression-free survival and OS durations were shorter in the patients with CA-125 levels of 11 to 35 U/mL and type II disease than in those with CA-125 levels of 10 U/mL or less and type I ovarian cancer.


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